The present invention relates to a process for preparing 1-indanones. It further pertains to the preparation of the corresponding indenes.
1-Indanones, which can be converted into the corresponding indene derivatives by known methods, are important intermediates in the synthesis of metallocene catalysts which typically are used in combination with a co-catalyst such as methylaluminoxane for the (co)polymerization of ethylenically unsaturated monomers, e.g., the production of isotactic polypropylene.
Several processes for preparing 1-indanones which start from either a propionic acid or an acrylic acid derivative are known in the art, but none of the prior art documents describe the process of the present invention.
For example, U.S. Pat. No. 5,840,948 describes a one-step process for preparing 1-indanones from benzene or a derivative thereof and a derivative of propionic acid carrying a leaving group in the (x-position using a Friedel-Crafts catalyst. The starting materials in this process typically contain two halogen atoms, preferably bromine or chlorine. In all examples, a dibrominated propionic acid derivative is used.
A disadvantage of the process of U.S. Pat. No. 5,840,948 is that the bromine or hydrobromic acid which results from the reaction presents a waste problem in terms of the presence and the amount of bromine-containing products.
DE 19637128 describes the reaction of an indane or tetralin derivative with a substituted acryloyl halide using a Friedel-Crafts catalyst.
A disadvantage of the process described in DE 19637128 is that the acryloyl-containing starting material is sensitive to dimerization and polymerization and that it is toxic.
R. W. Layer and I. R. MacGregor in the Journal of Organic Chemistry, Vol. 21, 1956, pp. 1120-1123, describe a process for the preparation of 1-indanones from xcex1-bromoaralkyl ketones. It is mentioned that xcex1-bromoaralkyl ketones are used because they are readily available. In the examples, bromine is used for preparing the xcex1-bromoaralkyl ketones.
As described above, the use of bromine and the formation of bromine-containing products presents a waste problem.
The process according to the present invention avoids these disadvantages, presents a solution to the waste problem, and allows for the preparation of 1-indanones in high yield and selectivity.
According to the present invention, a process is provided for preparing 1-indanones of formula I: 
and isomers thereof, wherein R1, R2, R3, R4, R5, and R6 independently represent H or a C1-C20 hydrocarbon group or R1 and R2 or R2 and R3 or R3 and R4 and/or R5 and R6 together with the carbon atoms to which they are attached form a saturated or unsaturated 5- or 6-membered ring, said hydrocarbon group and/or said ring optionally containing one or more hetero atoms, said ring optionally being substituted with a C1-C4 hydrocarbon group, said process comprising reacting a compound of formula II: 
wherein R1, R2, R3, R4, R5, and R6 have the same meaning as defined above, with a chlorinating agent, followed by reaction with a Friedel-Crafts catalyst.
It is to be noted that the regioselectivity of the ring closure reaction with the Friedel-Crafts catalyst is dependent on the presence or absence as well as the types of R-group substituents in the compound of formula II. It may be that more than one isomer is formed during this ring closure reaction, as can be seen in Example 3 described below. Hence, the invention process relates to 1-indanones of formula I and isomers thereof.
Suitable C1-C20 hydrocarbon groups include C1-C20 alkyl, C1-C10 alkoxy, C2-C20 alkenyl, C2-C20 alkynyl, C6-C20 aryl, C6-C20 aryloxy, C7-C20 arylalkyl, and C7-C20 alkylaryl groups, which groups optionally may contain one or more hetero atoms such as O, Si, and halogen atoms. Said groups may be linear or branched.
Preferably, R1, R2, R3, R4, R5, and R6 independently represent H or a C1-C20 alkyl group or R1 and R2 or R2 and R3 or R3 and R4 and/or R5 and R6 together with the carbon atoms to which they are attached form a saturated or unsaturated 5- or 6-membered ring, said ring optionally being substituted with a C1-C4 hydrocarbon group. More preferably, R1, R2, R3, R4, R5, and R6 independently represent H or a C1-C4 alkyl group or R1 and R2 or R2 and R3 or R3 and R4 and/or R5 and R6 together with the carbon atoms to which they are attached form a saturated or unsaturated 5- or 6-membered ring. Even more preferably, R1, R4, and R5 represent H, R2 and R3 together with the carbon atoms to which they are attached form a saturated 5- or 6-membered ring, and R6 represents H or a C1-C4 alkyl group. Most preferably, R6 represents a C1-C4 alkyl group.
A particularly preferred C1-C4 alkyl group is a methyl group.
Suitable starting materials of formula II are either commercially available or can be prepared by methods known to a person skilled in this art, such as by Friedel-Crafts acylation.
In the context of the present invention, it is well-known to a person skilled in the art what is meant by the term xe2x80x9cchlorinating agent.xe2x80x9d Chlorination of hydrocarbons is a common organic reaction and suitable chlorinating agents include chlorine, N-chlorosuccinimide, and sulfuryl chloride. For other suitable chlorinating agents the reader is referred to J. March, Advanced Organic Chemistry, Fourth Edition, John Wiley and Sons, New York, 1992, pp. 587-590. Preferred chlorinating agents are chlorine and sulfuryl chloride. In the process of the present invention most preferably sulfuryl chloride is used. Chlorine-containing salts that result from the chlorination reaction typically are discarded via the waste water. Surprisingly, the use of a chlorinating agent, in particular sulfuryl chloride, gave chlorinated products in a very high, nearly quantitative yield (see the Examples).
Typically, an acid or base catalyst in a conventional amount is used in the chlorination reaction. A practical acid catalyst is sulfuric acid, methanesulfonic acid or p-toluenesulfonic acid. A preferred chlorination catalyst is concentrated sulfuric acid.
Chlorination can be carried out in the absence or presence of a solvent. Suitable solvents include hydrocarbon solvents such as pentane, hexane, heptane, and toluene, and halogenated alkanes such as dichloromethane. Mixtures of solvents may also be used. Preferably, the reaction is carried out using a minimal amount of a solvent such as heptane.
An advantage of the present invention process is that it can be carried out at a relatively high concentration, which results in a higher reactor filling and a more economical process as compared to the processes of the prior art.
Chlorination can be carried out in a wide temperature range. Typically, it is performed at from 0xc2x0 C. up to 100xc2x0 C., preferably at from room temperature up to 100xc2x0 C. A preferred temperature range for carrying out the chlorination at pilot plant scale (typically carried out in a 1,000 liters reactor) is 50 to 70xc2x0 C.
Typically, the molar ratio of ketone (II) to chlorinating agent is 1:1 to 1:2. Preferably, it is 1:1 to 1:1.5, more preferably 1:1.1 to 1:1.2. Most preferably, a molar excess of about 10% of the chlorinating agent is used. Preferably, the excess of chlorinating agent is removed from the reaction productxe2x80x94in a conventional way, e.g., by evaporation or via destruction with waterxe2x80x94before further reaction.
Typical reaction times for the chlorination reaction are in the order of 15 minutes to 4 hours.
In the invention process, the chlorination reaction is followed by a ring closure reaction using a Friedel-Crafts catalyst.
Suitable Friedel-Crafts catalysts are known in the art and are described, for example, in J. March, Advanced Organic Chemistry, Fourth Edition, pp. 535-542 . Typically, these catalysts are Lewis acid catalysts. Examples of suitable catalysts include aluminium chloride and iron (III) chloride. A preferred catalyst is aluminium chloride.
Typically, the ring closure reaction is carried out in the presence of a conventional solvent. Suitable solvents are those which have been described above for the chlorination reactionxe2x80x94with the exception of toluenexe2x80x94and the same solvent or mixture of solvents may be used for the ring closure reaction. Preferably, a solvent comprising a halogenated alkane such as dichloromethane is used for the ring closure reaction. Mixtures of a hydrocarbon solvent such as heptane and a halogenated solvent such as dichloromethane are particularly suitable for carrying out the ring closure reaction. Preferably, the ring closure reaction is carried out in a mixture of the hydrocarbon solvent which has been used for the chlorination reaction, such as heptane, and a halogenated solvent such as dichloromethane.
The ring closure reaction can be carried out in a wide temperature range. Typically, it is performed at from 0xc2x0 C. up to 100xc2x0 C., in particular at from room temperature up to 100xc2x0 C. A practical temperature for carrying out the ring closure reaction at laboratory scale as well as at pilot plant scale is room temperature.
Typically, the molar ratio of Friedel-Crafts catalyst used in the invention process to ketone (II) is 1:1 to 3:1. Preferably, it is 1:1 to 1.5:1, more preferably 1.2:1 to 1.3:1.
A typical reaction time for the ring closure reaction is 15 minutes to 2 hours, although longer reaction times were observed in some experiments.
The invention process can be carried out using means and equipment well-known to a person skilled in this art.
The invention process is particularly suitable for preparing 2-substituted 1-indanones. Examples have been described below.
As is known to a person skilled in the art, the 1-indanones of formula I may be reduced to the corresponding indenes in an inert solvent in two reaction steps using a reducing agent and an acid dehydrating agent.
Thus, the present invention also pertains to a process for preparing indenes of formula III: 
and isomers thereof, wherein R1-R6 have the meaning described above and which process is characterized in that a compound of formula II is converted into a compound of formula I according to the process described above, followed by reaction in an inert solvent first with a reducing agent and then with an acid dehydrating agent according to methods known per se.
Suitable reducing agents include sodium borohydride, lithium aluminium hydride, diisobutylaluminium hydride (DIBAL-H), and sodium bis(2-methoxyethoxy)aluminium hydride. For these and other suitable reducing agents the reader is referred to J. March, Advanced Organic Chemistry, Fourth Edition, John Wiley and Sons, New York, 1992, pp. 910-918. A particularly preferred reducing agent is DIBAL-H.
Suitable acids include sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, and phosphoric acid. For these and other suitable acids the reader is referred to J. March, Advanced Organic Chemistry, Fourth Edition, John Wiley and Sons, New York, 1992, pp. 1011-1012. A particularly preferred acid is p-toluenesulfonic acid.
Suitable solvents include alkanes such as pentane, hexane, heptane, toluene, and xylene, halogenated alkanes such as dichloromethane and chloroform, and ethers such as tetrahydrofuran.
The present invention is illustrated by the following Examples.